Variant 2-20774826-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_021925.4(LDAH):c.452G>A(p.Arg151Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00946 in 1,612,958 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0096 ( 96 hom. )

Consequence

LDAH
NM_021925.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.341

Variant links:

Genes affected

LDAH (HGNC:26145): (lipid droplet associated hydrolase) Predicted to enable lipase activity. Predicted to be involved in lipid storage. Predicted to be located in endoplasmic reticulum. Predicted to be active in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

LDAH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031837225).

BP6

Variant 2-20774826-C-T is Benign according to our data. Variant chr2-20774826-C-T is described in ClinVar as [Benign]. Clinvar id is 789267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDAH	NM_021925.4 linkuse as main transcript	c.452G>A	p.Arg151Gln	missense_variant	4/7	ENST00000237822.8	NP_068744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDAH	ENST00000237822.8 linkuse as main transcript	c.452G>A	p.Arg151Gln	missense_variant	4/7	1	NM_021925.4	ENSP00000237822	P1	Q9H6V9-1

Frequencies

GnomAD3 genomes

AF:

0.00792

AC:

1205

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0275

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00841

AC:

2114

AN:

251274

Hom.:

AF XY:

0.00835

AC XY:

1134

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0269

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.00669

GnomAD4 exome

AF:

0.00962

AC:

14058

AN:

1460644

Hom.:

Cov.:

AF XY:

0.00936

AC XY:

6802

AN XY:

726650

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00302

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0244

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.00632

GnomAD4 genome

AF:

0.00791

AC:

1205

AN:

152314

Hom.:

Cov.:

AF XY:

0.00843

AC XY:

628

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0275

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00851

Hom.:

Bravo

AF:

0.00549

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00826

AC:

ExAC

AF:

0.00877

AC:

1065

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00802

EpiControl

AF:

0.00771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 09, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.52

DANN

Benign

0.97

DEOGEN2

Benign

0.044

.;.;T;T;T;T;T;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.053

LIST_S2

Uncertain

0.86

.;D;T;T;D;T;T;D;T;T

MetaRNN

Benign

0.0032

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N;N;N;N;N

PROVEAN

Benign

-1.3

.;N;N;.;N;N;N;.;N;N

REVEL

Benign

0.047

Sift

Benign

0.054

.;T;T;.;T;D;D;.;T;T

Sift4G

Benign

0.34

T;T;T;T;T;T;T;T;.;.

Polyphen

0.80, 0.64, 0.48

.;.;P;.;.;P;P;.;.;.

Vest4

0.28

MVP

0.43

MPC

0.26

ClinPred

0.010

GERP RS

-5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over